Molecular genetic mechanisms responsible for the development and progression of many cancers remain largely unknown. Identification of sites of frequent and recurring allelic deletion or gain is a first step toward identifying some of the important genes involved in the malignant process. Previous studies in retinoblastoma (Friend, et al. Nature, 323:643-6 (1986)) and other cancers (Cawthon, et al., Cell, 62:193-201 (1990); Baker, et al., Science, 244:217-21 (1989); Shuin, et al., Cancer Res, 54:2832-5 (1994)) have amply demonstrated that definition of regional chromosomal deletions occurring in the genomes of human tumors can serve as useful diagnostic markers for disease and are an important initial step towards identification of critical genes. Similarly, regions of common chromosomal gain have been associated with amplification of specific genes (Visakorpi, et al., Nature Genetics, 9:401-6 (1995)).
Comparative genomic hybridization (CGH) is a relatively new molecular technique used to screen DNA from tumors for regional chromosomal alterations (Kallioniemi, et al., Science, 258:818-21 (1992) and WO 93/18186). Unlike microsatellite or Southern analysis allelotyping studies, which typically sample far less than 0.1% of the total genome, a significant advantage of CGH is that all chromosome arms are scanned for losses and gains. Moreover, because CGH does not rely on naturally occurring polymorphisms, all regions are informative, whereas polymorphism-based techniques are limited by homozygous (uninformative) alleles among a fraction of tumors studied at every locus.
Increases in copy number in the long arm of chromosome 3, in particular 3q25-3qter, has been associated with cancer. Increases in copy number in this area have been seen not only in ovarian tumors (Iwabuchi et al., Cancer Research 55:6172-8180 (1995) and Arnold et al., Genes Chromosomes Cancer 16:46-54 (1996)) but also in brain tumors, head and neck cancer, lung cancer, ductal breast cancer, renal cell and other urinary tract cancers, and cervical cancer. Ried et al., Genes Chromosomes Cancer 15:234-245 (1996); Yeatman et al. Clin Exp Metastasis 14:246-252 (1996); Brzoska et al., Cancer Res 15:3055-3059 (1995); Ried et al., Cancer Res 54:1801-1806 (1994); Cher et al. Cancer Research 56:3091-3102 (1996); Heselmeyer et al., Proc. Natl. Acad. Sci. USA 93:479-484 (1996); Levin et al. Genes Chromosomes Cancer 13:175-185 (1995); and Speicher et al., Cancer Res 55:1010-3 (1995).
The identification of narrower regions of genetic alteration or genes associated with cancers such as ovarian cancer would be extremely useful in the early diagnosis or prognosis of these diseases. The present invention addresses these and other needs.